Abstract:

Background: Familial Mediterranean Fever (FMF) is the most common auto-inflammatory disease characterized by recurrent attacks. FMF was found to be correlated with the mutation in MEFV gene. The mutation in the MEFV gene located at the short arm of the 16th chromosome impairs the encoding of the pyrin protein. Until now, numerous variants of the MEFV gene have been identified. Patients with M694V homozygous mutation have been reported to have a more severe disease. However, there is no clear study of clinical correlation in other variants. In this study, we aimed to investigate the frequency and clinical correlation of MEFV gene variants.   Methods: Electronic medical records of FMF cohort were retrospectively analyzed. FMF cohort was established in year 2010 and since then all patients who fulfilled Tel-Hashomer criteria Demographic information, attack characteristics, treatment information and MEFV gene outcomes of the patients were analysed using the records. In MEFV gene analysis, M694V, M694I, M680I, V726A, R761H, A744S, F479L, P369S, R202Q and E148Q variants are evaluated.   Results: A total of 605 patients were included in the study. In patients who had M694V mutation, arthritis and erysipelas were observed more frequently (p=0.04, p=0.008). Increased family history of FMF was identified in patients with M694V mutation (p<0.001).  In patients with M694V mutation, it was found that age of onset of FMF symptoms, age of diagnosis, and age of treatment initiation were younger (p=0.003, p=0.014, p=0.025). In patients with M694V homozygous, frequency of amyloidosis was higher (p<0.001). The risk of developing amyloidosis was higher in M694V homozygous (Odds ratio 7.46, 95% confidence interval: 2.92-19.05). Conclusions: In conclusion, homozygous M694V mutation leads to severe disease. There was no clinical variability in other MEFV gene variants.

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